Soluble klotho as an effective biomarker to characterize inflammatory states

Ann Med. 2022 Dec;54(1):1520-1529. doi: 10.1080/07853890.2022.2077428.


Background & aims: Soluble α-Klotho (s-Klotho) is a circulating protein with pleiotropic effects that mainly induce protective effects. Our study investigates the associations between s-Klotho and several established inflammatory biomarkers, with the aim of examining whether s-Klotho levels are representative of inflammatory states.

Methods: A total of 11,128 eligible participants from NHANES 2007-2016 were included in our study. Levels of four inflammatory biomarkers, uric acid (UA), C-reactive protein (CRP), white blood cell (WBC) count, and mean platelet volume (MPV), were examined for their relationship with s-Klotho levels. Sub-analyses sorted the total population by gender and into four quartiles. Linear regression models were used to evaluate the strengths of associations.

Results: All four inflammatory biomarkers were significantly associated with s-Klotho levels. UA, CRP, and WBC count showed an inverse association, while MPV showed a direct one. Of the four markers, UA was most strongly correlated with s-Klotho levels (β coefficient: -28.89 in unadjusted model, p<.001), and this relationship was stronger in women than in men (β coefficient of UA in men: -22.01, p<.001; in women: -31.54, p<.001). In addition, all four biomarkers manifested stronger associations with s-Klotho in higher quartiles, and the highest absolute values of β coefficients appeared in Q4 vs. Q1.

Conclusion: s-Klotho is significantly associated with well-recognized inflammatory biomarkers. A decrease in s-Klotho levels implies a general inflammatory status; therefore, s-Klotho serves as a potential biomarker that is inversely correlated with inflammatory conditions. Further applications in clinical practice will provide us with a better understanding of its role.Key messagesSoluble α-Klotho (s-Klotho) levels are significantly associated with the inflammatory markers uric acid, C-reactive protein, white blood cell count, and mean platelet volume.S-Klotho is involved in inflammatory processes and plays a protective role.S-Klotho may serve as an inverse indicator of inflammation.

Keywords: C-reactive protein; Soluble Klotho; biomarker; inflammation; uric acid.

MeSH terms

  • Biomarkers
  • C-Reactive Protein* / metabolism
  • Female
  • Humans
  • Klotho Proteins
  • Male
  • Nutrition Surveys
  • Uric Acid*


  • Biomarkers
  • Uric Acid
  • C-Reactive Protein
  • Klotho Proteins